1. Field of the Invention
This invention relates to a method for enhancing the unrolling of a controlled release active agent-containing polymer matrix device in an aqueous environment, the device being constrained in a rolled configuration prior to placement in said environment. More particularly, it relates to a method for enhancing the unrolling of such an active agent-containing polymer matrix device, including a laminate device, in an aqueous environment, the device being constrained in a rolled configuration prior to placement in said environment which comprises coating one side of the device with an elastomer prior to constraining it in a rolled configuration.
2. Description of the Prior Art
Administration of an active agent to a use environment in such a manner that the agent is released in a controlled manner over a prolonged period of time is well known in the veterinary pharmaceutical and medical arts. A large variety of devices have been developed for achieving the desired result. Representative of such devices of value for use in a mammalian system, and especially in ruminant animals, are variable geometry devices of the polymer matrix type. Particularly valuable for use in ruminant animals are matrix type devices having a size and composition which permit them to be constrained to a size and shape suitable for oral administration to a mammal and which, when in the use environment, revert to their original or near-original pre-constrained shape. Included in the term matrix devices as used herein are laminated matrix devices.
Variable geometry matrix devices of the type referred to above are disclosed in U.S. Pat. No. 4,228,149, issued Oct. 14, 1980. Laminate devices comprising an active agent containing resilient polymeric sheet and a polymer film coating one or both sides of said sheet are also disclosed in said patent. Perforated laminate devices are described in U.S. Pat. No. 4,601,893, issued July 22, 1986. The disclosures of each of said patents is incorporated herein by reference.
Preferred matrix devices of the non-laminate type of U.S. Pat. No. 4,228,149, referred to herein as "simple" matrix devices, are those wherein the device comprises a resilient sheet of ethylene vinylacetate (EVA) copolymer as the medium in which the active agent is dispersed. Preferred laminate type devices described in said patent are those wherein the active agent-containing sheet is coated on one or both surfaces with EVA, but not on the edges.
Preferred laminate devices of U.S. Pat. No. 4,601,893 are those wherein the active agent-containing core sheet is EVA. Particularly preferred are those devices wherein the core sheet is coated on both surfaces by films of EVA.
The devices described in the above-cited patents, all oral delivery devices for controlled release of an active agent to a ruminant animal are, as initially manufactured, generally rectangular in shape. To permit their oral administration they are rolled to a cylindrical or substantially cylindrical shape; i.e., a rolled configuration, and constrained in such shape by constraining means. For this reason, the flexibility, and especially the resiliency, of the polymer sheet which comprises the matrix or the core sheet of a laminate device are important as regards the ability of the constrained device to unroll in the use environment, e.g., the rumeno-reticular sac, once the constraining means operates to release the constrained laminate.
Suitable constraining means are, for example, biodegradable string, tape or glue, water soluble adhesive, paper or gelatin capsules.
The herein-described devices can be used to administer a variety of drugs to ruminants. Representative of the active agents which can be used in the devices described herein are anthelmintics, antibacterials, beta-lactams, aminoglycosides, antibacterial growth promotants, antiparasitic agents, essential minerals, vitamins, sulfa drugs, larvacides and insecticides.
The devices described herein offer a practical and especially valuable means for the control (therapeutic and prophylactic) of helminth infections in ruminant animals, cattle in particular. For this purpose anthelmintics, including salts thereof, such as morantel, pyrantel, levamisole, tetramisole, oxantel, ivermectin, piperazine and diethyl carbamazine are of great value.
The constrained devices when placed within the use environment should unroll to their original or near-original rectangular shape so as to permit retention of the device in the rumeno-reticular sac for a prolonged period. However, upon prolonged storage in a constrained shape they tend to set; i.e., to lose their resiliency, and the ability to unroll to a cross-section diameter within a relatively brief period, about two hours, following their administration sufficient to ensure their retention in the rumenoreticular sac and to prevent regurgitation of the device. Thus, the matrix devices of the art undergo an aging process, which process is a function of time and temperature, which reduces their ability to unroll in the use environment, e.g., the rumen, to a size adequate for retention.